The Clinical Epilepsy Section is using a multimodality approach, with an emphasis on neuroimaging techniques, including positron emission tomography (PET) and magnetic resonance imaging (MRI),to evaluate patients with severe epilepsy. PET uses radiolabelled tracers to measure cerebral glucose metabolism, blood flow, and neurotransmitter distribution. Focal hypometabolism may underlie epileptogenic zones. During seizures, increased glucose utilization and blood flow are found. We examined the course of alterations in glucose metabolism in patients with intractable partial epilepsy. The most dramatic changes occurred in the inferior temporal regions. Effects up to 48 hr were found after simple partial seizures (SPS) and complex partial seizures (CPS). However, the time course was different for the two types of seizures. The inferior temporal metabolic rate ipsilateral to focus was relatively increased compared with interictal rate in the 24- hr period following a SPS. A nadir occurred in the second 24 hr following a SPS. The rate then rose to an intermediate level after 48 hr. The relative regional increase in ipsilateral metabolism following a CPS persisted for 48 hr before falling. The brain may take longer than 24 hr after a partial seizure to return to its baseline state. Children with partial seizures are followed with serial PET scans to assess the development of hypometabolism in the epileptic focus. Magnetoencephalography (MEG). may have the potential to accurately localize the subsurface origin of spikes. EEG provides little information on the spatial distribution of epileptiform discharges in cortical depths; MEG may be superior. Digital signal processing is being applied to data from multiple closely spaced electrode arrays. Comparison of invasive localization of epileptic foci using subdural electrodes and noninvasive evaluation is being performed. Seizures in animal models are used to study patterns of neuronal damage and their relation to altered electrophysiology. Somatostatin (SS) neurons are selectively lost in the dentate hilus of patients with longstanding temporal lobe epilepsy. These neurons are vulnerable to non-NMDA but not NMDA-mediated neurotoxicity in cell culture. NBQX, a non-NMDA antagonist, protected against loss of SS as well as neuropeptide Y (NPY)-containing neurons, while MK-801 protected only against the former. Paired-pulse inhibition was lost in both experimental groups. SS and NPY immunoreactive neurons may not be responsible for this type of inhibition. Nitric oxide (NO) synthase inhibitors may increase seizure severity by disrupting cerebral blood flow autoregulation.